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Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic st...

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Autores principales: Ginsberg, Henry N, Packard, Chris J, Chapman, M John, Borén, Jan, Aguilar-Salinas, Carlos A, Averna, Maurizio, Ference, Brian A, Gaudet, Daniel, Hegele, Robert A, Kersten, Sander, Lewis, Gary F, Lichtenstein, Alice H, Moulin, Philippe, Nordestgaard, Børge G, Remaley, Alan T, Staels, Bart, Stroes, Erik S G, Taskinen, Marja-Riitta, Tokgözoğlu, Lale S, Tybjaerg-Hansen, Anne, Stock, Jane K, Catapano, Alberico L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670783/
https://www.ncbi.nlm.nih.gov/pubmed/34472586
http://dx.doi.org/10.1093/eurheartj/ehab551
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author Ginsberg, Henry N
Packard, Chris J
Chapman, M John
Borén, Jan
Aguilar-Salinas, Carlos A
Averna, Maurizio
Ference, Brian A
Gaudet, Daniel
Hegele, Robert A
Kersten, Sander
Lewis, Gary F
Lichtenstein, Alice H
Moulin, Philippe
Nordestgaard, Børge G
Remaley, Alan T
Staels, Bart
Stroes, Erik S G
Taskinen, Marja-Riitta
Tokgözoğlu, Lale S
Tybjaerg-Hansen, Anne
Stock, Jane K
Catapano, Alberico L
author_facet Ginsberg, Henry N
Packard, Chris J
Chapman, M John
Borén, Jan
Aguilar-Salinas, Carlos A
Averna, Maurizio
Ference, Brian A
Gaudet, Daniel
Hegele, Robert A
Kersten, Sander
Lewis, Gary F
Lichtenstein, Alice H
Moulin, Philippe
Nordestgaard, Børge G
Remaley, Alan T
Staels, Bart
Stroes, Erik S G
Taskinen, Marja-Riitta
Tokgözoğlu, Lale S
Tybjaerg-Hansen, Anne
Stock, Jane K
Catapano, Alberico L
author_sort Ginsberg, Henry N
collection PubMed
description Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD.
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spelling pubmed-86707832021-12-15 Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society Ginsberg, Henry N Packard, Chris J Chapman, M John Borén, Jan Aguilar-Salinas, Carlos A Averna, Maurizio Ference, Brian A Gaudet, Daniel Hegele, Robert A Kersten, Sander Lewis, Gary F Lichtenstein, Alice H Moulin, Philippe Nordestgaard, Børge G Remaley, Alan T Staels, Bart Stroes, Erik S G Taskinen, Marja-Riitta Tokgözoğlu, Lale S Tybjaerg-Hansen, Anne Stock, Jane K Catapano, Alberico L Eur Heart J Special Article Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD. Oxford University Press 2021-09-02 /pmc/articles/PMC8670783/ /pubmed/34472586 http://dx.doi.org/10.1093/eurheartj/ehab551 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Special Article
Ginsberg, Henry N
Packard, Chris J
Chapman, M John
Borén, Jan
Aguilar-Salinas, Carlos A
Averna, Maurizio
Ference, Brian A
Gaudet, Daniel
Hegele, Robert A
Kersten, Sander
Lewis, Gary F
Lichtenstein, Alice H
Moulin, Philippe
Nordestgaard, Børge G
Remaley, Alan T
Staels, Bart
Stroes, Erik S G
Taskinen, Marja-Riitta
Tokgözoğlu, Lale S
Tybjaerg-Hansen, Anne
Stock, Jane K
Catapano, Alberico L
Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title_full Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title_fullStr Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title_full_unstemmed Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title_short Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society
title_sort triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the european atherosclerosis society
topic Special Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670783/
https://www.ncbi.nlm.nih.gov/pubmed/34472586
http://dx.doi.org/10.1093/eurheartj/ehab551
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